PK/PD EVALUATION OF THE NOVEL ATYPICAL OPIOID TAPENTADOL IN YELLOW-BELLIED SLIDER TURTLES (TRACHEMYS SCRIPTA SCRIPTA)

摘要

Opioids are considered the most effective drugs for controlling\udpain in mammals, but in reptiles, opioid drug administration\udhas yielded unexpected results with respect to analgesia (1–3).\udTapentadol (TAP) is a novel atypical opioid drug labeled for\udhuman use. It has shown in humans an equivalent analgesic\udactivity than that of morphine, and a reduction in the rate of\udadverse effects. If the reduction in adverse effects observed in\udhumans holds true in reptiles, TAP could be an attractive analgesic\udoption.\udThe aim of this study was to evaluate the pharmacokinetics\udand the pharmacodynamics of TAP in yellow-bellied slider,\udafter a single intramuscular injection of 5 mg kg\ud1.\udTurtles (n = 9) were randomly assigned to two treatment\udgroups, according to a single-dose, single-treatment, unpaired,\udtwo-period crossover design. Group A (n = 5) received a single\udIM (proximal front limb) dose of TAP (5 mg ml\ud1) at\ud5 mg kg\ud1. Group B (n = 4) received a single IM injection of\udsaline (equivalent volume to opioid volumes) of TAP at the\udsame site. After a 1-month washout period, groups were\udrotated and the experiment repeated. Blood samples (1 ml)\udwere collected from the subcarapacial venipuncture site at 0,\ud1, 2, 4, 6, 10, and 24, h and TAP plasma concentrations\uddetermined by a validated HPLC-FL method. At the same time\udof the blood collections an infrared thermal stimuli (70°C) was\udapplied to the plantar surface of the turtles’ hind limbs to evaluate\udthe thermal withdrawal latency (TWL). The thermal antinociceptive\udeffect was expressed as Maximum Possible\udResponse (% MPR).\udTAP plasma concentrations were detectable between 1 and\ud24 h (1619–37 ng ml\ud1, respectively). The TAP treated group\udshowed an increase in TWL 1 h after drug administration\ud(13.32 6.40 s). Subsequently, TWL decreased with time, significant\uddifferences between treatment and control groups were\udapparent up to 10 h following treatment. Mean MPR increased\udto a maximum of 46.68 12.30% at 1 h and decreased to a\udminimum of 1.62 2.77% at 24 h. The MPR difference\udbetween TAP and saline group was significant up to 10 h. A\udlinear relationship (r2 = 0.99) between TAP plasma concentration\udand effect was found. Given these findings, TAP appears to be an attractive option\udfor antinociception in turtles, due to its rapid onset and acceptable\udduration of effect.